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Context: The risk of cerebral venous thrombosis at particular locations and its association with high altitude is yet to be established completely. The relation between high altitude and venous thromboembolic events has been debated for many years. Cerebral venous thrombosis presenting with nonspecific symptoms like headache can be a tough challenge for primary care physicians deployed at high altitudes. Materials and Methods: Combatants going to wide areas of mountainous territories at varying altitudes presenting with persistent severe headache associated with nausea and vomiting were subjected into the study after evaluation at zonal and tertiary care hospital. Results: Over a period of 18 months from October 2018 to March 2020, 75 cases of headache were screened and evaluated. Eighteen of these patients were diagnosed to have cerebral venous thrombosis. Conclusion: The occurrence of chronic venous thrombosis in combatants who enter and remain at high altitude for the prolonged duration is very common and the gold standard for diagnosis is a clinical evaluation with radio imaging.

Corneal scarring, a significant cause of global blindness, results from various insults, including trauma, infections, and genetic disorders. The conventional treatment to replace scarred corneal tissues includes partial or full-thickness corneal transplantation using healthy donor corneas. However, only 1 in 70 individuals with treatable corneal scarring can undergo surgery, due to the limited supply of transplantable donor tissue. Our research focuses on cell-based strategies, specifically ex vivo–expanded corneal stromal stem cells (CSSCs), to address corneal scarring. Preclinical studies have demonstrated the efficacy of CSSC treatment in reducing corneal inflammation and fibrosis, inhibiting scar formation, and regenerating native stromal tissue. Mechanisms include CSSC differentiation into stromal keratocytes and the expression of regenerative cytokines. Here, we present a good manufacturing practice (GMP)-compliant protocol to isolate and expand human CSSCs. This method paves the way to produce clinical-grade CSSCs for transplantation and clinical trials.

Abstract Background Anterior uveitis, inflammation of the anterior chamber and related structures, is a cohort of diseases that can present to almost any general or sub-specialty Ophthalmology practice. Its features classically involve anterior chamber cell and flare. Below the surface of these two signs exist a panoply of diagnoses. Body The purpose of this review is to provide a general framework for diagnoses of anterior uveitis that are often missed as well as non-uveitic pathologies that often mimic anterior uveitis. Diagnostic deviation in either direction can have vision-threatening and rarely life-threatening consequences for patients. Using a comprehensive literature review we have collected a broad spectrum of etiologies of anterior uveitis that are easily missed and non-uveitic pathologies that can masquerade as anterior uveitis. Conclusions We present a focused review on specific misdiagnosed anterior uveitis pathologies and some of the conditions that can masquerade as anterior uveitis and scleritis.

Abstract Background Mesenchymal stem cells in the adult corneal stroma (named corneal stromal stem cells, CSSCs) inhibit corneal inflammation and scarring and restore corneal clarity in pre-clinical corneal injury models. This cell therapy could alleviate the heavy reliance on donor materials for corneal transplantation to treat corneal opacities. Herein, we established Good Manufacturing Practice (GMP) protocols for CSSC isolation, propagation, and cryostorage, and developed in vitro quality control (QC) metric for in vivo anti-scarring potency of CSSCs in treating corneal opacities. Methods A total of 24 donor corneal rims with informed consent were used—18 were processed for the GMP optimization of CSSC culture and QC assay development, while CSSCs from the remaining 6 were raised under GMP-optimized conditions and used for QC validation. The cell viability, growth, substrate adhesion, stem cell phenotypes, and differentiation into stromal keratocytes were assayed by monitoring the electric impedance changes using xCELLigence real-time cell analyzer, quantitative PCR, and immunofluorescence. CSSC’s conditioned media were tested for the anti-inflammatory activity using an osteoclastogenesis assay with mouse macrophage RAW264.7 cells. In vivo scar inhibitory outcomes were verified using a mouse model of anterior stromal injury caused by mechanical ablation using an Algerbrush burring. Results By comparatively assessing various GMP-compliant reagents with the corresponding non-GMP research-grade chemicals used in the laboratory-based protocols, we finalized GMP protocols covering donor limbal stromal tissue processing, enzymatic digestion, primary CSSC culture, and cryopreservation. In establishing the in vitro QC metric, two parameters—stemness stability of ABCG2 and nestin and anti-inflammatory ability (rate of inflammation)—were factored into a novel formula to calculate a Scarring Index (SI) for each CSSC batch. Correlating with the in vivo scar inhibitory outcomes, the CSSC batches with SI 10 were ineffective to inhibit scarring. Conclusions We established a full GMP-compliant protocol for donor CSSC cultivation, which is essential toward clinical-grade cell manufacturing. A novel in vitro QC–in vivo potency correlation was developed to predict the anti-scarring efficacy of donor CSSCs in treating corneal opacities. This method is applicable to other cell-based therapies and pharmacological treatments.

Background: An overlooked factor in the efficacy of topical antibiotics to treat bacterial keratitis is the state of the corneal epithelium. Recently, we evaluated topical cefiderocol for the treatment of extensively drug-resistant (XDR) Pseudomonas aeruginosa (PA) keratitis in eyes with the corneal epithelium abraded. The goal of this study was to use the same model with the corneal epithelium left intact to evaluate the efficacy of cefiderocol and other antibiotics and compare the results to those of the previous study. Methods: NZW rabbit corneas with intact epithelium were inoculated with XDRPA. After 16 h, the rabbits were topically treated with cefiderocol 50 mg/mL, ciprofloxacin 0.3%, tobramycin 14 mg/mL, or saline. Following 8 h of treatment, the corneas were harvested for CFU determinations and cefiderocol concentrations. Results: Only cefiderocol significantly decreased CFU of the XDRPA strain compared with saline. The CFU in the cefiderocol and tobramycin-treated corneas for the XDRPA strain with initially intact epithelium were 1.83–1.4 Log10 greater than those produced in corneas with the abraded epithelium (p < 0.05). Cefiderocol concentrations were 5.02× less in corneas with initially intact epithelium. Conclusions: The efficacy of cefiderocol and tobramycin to treat experimental XDRPA keratitis is dependent on the state of the corneal epithelium.

Abstract Background To compare the rate of fractional change for multiple corneal tomographic factors in progressive keratoconus (KC). Methods In this retrospective case series, 40 eyes (40 patients) with progressive KC (increase in central keratometry of 1.00 D or maximum keratometry of 1.50 D on two visits at least six months apart) were included. Cases with previous history of ocular surgery, poor scans, corneal scars, severe dry eyes, post-excimer ectasia, pellucid marginal degeneration were excluded. Medical records, corneal tomography and anterior corneal wavefront (8 mm) (Scheimpflug tomography, Pentacam, Oculus, Germany) were analyzed. Rate of fractional change (Rx = (x1 − x0)/(|x0|tm)); where, x1 = value at follow-up, x0 = value at initial visit and tm = time in months, was measured. Results The mean age of the patients was 30.0 ± 8.4 years. The mean follow-up duration was 8.9 ± 4.2 months. Coma (0.076 ± 1.4) had the largest rate of fractional change (P = 1.7 × 10−14, Kruskal–Wallis test). The rate of fractional change was higher for aberrometric parameters (anterior corneal higher-order aberrations root mean square and anterior coma) compared to pachymetric and keratometric parameters (P values ranging from 1.4 × 10−4 to 7.4 × 10−10, Mann–Whitney test, effect size ranging from 0.4–0.7). The rate of fractional change was comparable between pachymetric and keratometric factors (P > 0.05 for all comparisons, Mann–Whitney test). Conclusions Anterior corneal wavefront, especially anterior coma, were noted to have higher rate of fractional change compared to single point keratometric and pachymetric indices in progressive KC. This information can be used for decision-making when monitoring patients with KC.

Introduction: Corneal blindness due to scarring is treated with corneal transplantation. However, a global problem is the donor material shortage. Preclinical and clinical studies have shown that cell-based therapy using corneal stromal stem cells (CSSCs) suppresses corneal scarring, potentially mediated by specific microRNAs transported in extracellular vesicles (EVs). However, not every CSSC batch from donors achieves similar anti-scarring effects. Objectives: To examine miRNA profiles in EVs from human CSSCs showing “healing” versus “non-healing” effects on corneal scarring and to design a tool to select CSSCs with strong healing potency for clinical applications. Methods: Small RNAs from CSSC-EVs were extracted for Nanostring nCounter Human miRNA v3 assay. MicroRNAs expressed > 20 folds in “healing” EVs (P

Purpose: To evaluate the outcomes of transepithelial corneal collagen crosslinking (CXL) for management of corneal ectasia after laser-assisted in situ keratomileusis (LASIK). Methods: CXL was performed on 18 eyes of 16 patients either with LASIK flap lift (n = 9; 365 nm, 30 mW/cm2, 4 minutes, pulse) or with transepithelial flap-on (n = 9 eyes; 365 nm, 3 mW/cm2, 30 minutes) technique. Postoperative change in maximum keratometry (Kmax), anterior elevation, posterior elevation, spherical equivalent (SE), logMAR uncorrected distance visual acuity (UDVA), aberrations, and central corneal thickness (CCT) were evaluated at 12 months postoperatively. Results: A total of 18 eyes of 16 patients (11 males, 5 females) were included. Overall, Kmax flattened more after flap-on CXL (P = 0.014) compared to flap-lift CXL. The endothelial cell density and posterior elevation were stable throughout the follow-up period. Index of vertical asymmetry (IVA), keratoconus index (KI), and central keratoconus index (CKI) decreased after flap-on CXL at 12 months, postoperatively (P < 0.05), whereas there were no statistically significant changes in these parameters after flap-off CXL group. The spherical aberrations and total root mean square decreased after flap-lift CXL at 12 months, postoperatively (P < 0.05). Conclusion: In our study, transepithelial collagen crosslinking was successfully used to halt disease progression in post-LASIK keratectasia. We recommend flap-on surgical technique for these cases.

Acanthamoeba keratitis (AK) is an intractable infection of the cornea. Penetrating keratoplasty is widely used for the management of severe AK but suffers from complications like graft rejection, endophthalmitis, and glaucoma. Herein, we aimed to describe the surgical technique and the results of elliptical deep anterior lamellar keratoplasty (eDALK) for the management of severe AK. In this retrospective case series, records of consecutive patients with AK poorly responsive to medical treatment who underwent eDALK from January 2012 to May 2020 were reviewed. The largest diameter of infiltration was ≥8 mm and did not involve the endothelium. The recipient bed was made by an elliptical trephine, and big bubble or wet-peeling technique was performed. Postoperative best spectacle-corrected visual acuity, endothelial cell density, corneal topographic data, and complications were evaluated. Thirteen eyes of thirteen patients (eight men and five women, 45.54 ± 11.78 years old) were included in this study. The mean follow-up interval was 21.31 ± 19.59 months (range, 12–82 months). At the last follow-up, the mean best spectacle-corrected visual acuity was 0.35 ± 0.27 logarithm of the minimum angle of resolution. The mean refractive and topographic astigmatism were − 3.21 ± 1.77 and 3.08 ± 1.14 D, respectively. Intraoperative perforation was encountered in one case and double anterior chambers occurred in two cases. One graft developed stromal rejection and one eye developed amoebic recurrence. eDALK can serve as the first-line surgical management of severe AK poorly responsive to medical treatment.

Dry eye disease encompasses a broad range of etiologies and disease subtypes which have similar clinical manifestations. Medications can cause dry eye disease or symptoms of dryness as a side effect by either interfering with the lacrimal gland or meibomian gland function, or both, and by other mechanisms that affect the ocular surface homeostasis. This is important to know and recognize as eliminating the offending medication can reverse the symptoms and, in many cases, prevent further deterioration of the ocular surface inflammation. This review focuses on drugs like systemic isotretinoin and taxanes, which cause meibomian gland dysfunction; immune checkpoint inhibitors that cause lacrimal gland dysfunction; gliptins and topical antiglaucoma medications that cause cicatrizing conjunctivitis; and epidermal growth factor receptor inhibitors, fibroblast growth factor receptor inhibitors, and belantamab mafodotin, which cause mucosal epitheliopathy. Many of these medications, particularly the newer anticancer agents, have only recently been introduced for clinical use, and knowledge and awareness of their ocular side effects are still evolving. This review aims to update ophthalmologists on the drug-induced causes of dry eye disease or symptoms of dryness, which is avoidable by discontinuation of the incriminating agent or can be mitigated by reducing the dose or frequency of usage.

Abstract Background The evaluation of refraction is indispensable in ophthalmic clinics, generally requiring a refractor or retinoscopy under cycloplegia. Retinal fundus photographs (RFPs) supply a wealth of information related to the human eye and might provide a promising approach that is more convenient and objective. Here, we aimed to develop and validate a fusion model-based deep learning system (FMDLS) to identify ocular refraction via RFPs and compare with the cycloplegic refraction. In this population-based comparative study, we retrospectively collected 11,973 RFPs from May 1, 2020 to November 20, 2021. The performance of the regression models for sphere and cylinder was evaluated using mean absolute error (MAE). The accuracy, sensitivity, specificity, area under the receiver operating characteristic curve, and F1-score were used to evaluate the classification model of the cylinder axis. Results Overall, 7873 RFPs were retained for analysis. For sphere and cylinder, the MAE values between the FMDLS and cycloplegic refraction were 0.50 D and 0.31 D, representing an increase of 29.41% and 26.67%, respectively, when compared with the single models. The correlation coefficients (r) were 0.949 and 0.807, respectively. For axis analysis, the accuracy, specificity, sensitivity, and area under the curve value of the classification model were 0.89, 0.941, 0.882, and 0.814, respectively, and the F1-score was 0.88. Conclusions The FMDLS successfully identified the ocular refraction in sphere, cylinder, and axis, and showed good agreement with the cycloplegic refraction. The RFPs can provide not only comprehensive fundus information but also the refractive state of the eye, highlighting their potential clinical value.

IntroductionPseudomonas aeruginosa causes vision threatening keratitis. The LasR transcription factor regulates virulence factors in response to the quorum sensing molecule N-3-oxo-dodecanoyl-L-homoserine lactone. P. aeruginosa isolates with lasR mutations are characterized by an iridescent high sheen phenotype caused by a build-up of 2-heptyl-4-quinolone. A previous study demonstrated 22% (n=101) of P. aeruginosa keratitis isolates from India between 2010 and 2016 were sheen positive lasR mutants, and the sheen phenotype correlated with worse clinical outcomes for patients. In this study, a longitudinal collection of P. aeruginosa keratitis isolates from Eastern North America were screened for lasR mutations by the sheen phenotype and sequencing of the lasR gene.MethodsKeratitis isolates (n=399) were classified by sheen phenotype. The lasR gene was cloned from a subset of isolates, sequenced, and tested for loss of function or dominant-negative status based on an azocasein protease assay. A retrospective chart review compared outcomes of keratitis patients infected by sheen positive and negative isolates.ResultsA significant increase in sheen positive isolates was observed between 1993 and 2021. Extracellular protease activity was reduced among the sheen positive isolates and a defined lasR mutant. Cloned lasR alleles from the sheen positive isolates were loss of function or dominant negative and differed in sequence from previously reported ocular lasR mutant alleles. Retrospective analysis of patient information suggested significantly better visual outcomes for patients infected by sheen positive isolates.DiscussionThese results indicate an increase in lasR mutations among keratitis isolates in the United States and suggest that endemic lasR mutants can cause keratitis.

Abstract We employed the mechanical effect from 40 kHz ultrasound (US) to improve the delivery of riboflavin into corneal stroma for collagen crosslinking, which can benefit the treatment of keratoconus and other corneal ectasias. Experiments were conducted, first with porcine corneas ex vivo and then with New Zealand white rabbits in vivo, at varying mechanical index (MI) and sonication time. Results showed that 15 min of US applied on the cornea at MI = 0.8 in the presence of 0.5% of riboflavin solution enabled its delivery to deeper corneal stroma. Excessive heat was removed by a cooling setup to negate the thermal effect. The corneal absorption amount and penetration of riboflavin through cornea as detected by fluorotron, as well as the enhancement of corneal stiffness as measured by Young's modulus, were comparable to the conventional approach that requires complete corneal epithelium debridement. Histological analysis revealed minor exfoliation of superficial cell layers of corneal epithelium and loss of ZO‐1 tight junctions immediately after US. Full recovery of the corneal epithelium and restoration of tight junctions occurred in 3–4 days. The study shows that low‐intensity low‐frequency ultrasound (LILF US) is a less invasive alternative to the conventional epithelium‐off method for delivering riboflavin into the corneal stroma.

IntroductionAntibiotic resistance in bacterial species constitutes a growing problem in the clinical management of infections. Not only does it limit therapeutic options, but application of ineffective antibiotics allows resistant species to progress prior to prescribing more effective treatment to patients. Methicillin resistance in Staphylococcus aureus is a major problem in clinical infections as it is the most common hospital acquired infection.MethodsWe developed a photoacoustic flow cytometer using engineered bacteriophage as probes for rapid determination of methicillin resistance in Staphylococcus aureus with thirteen clinical samples obtained from keratitis patients. This method irradiates cells under flow with 532 nm laser light and selectively generates acoustic waves in labeled bacterial cells, thus enabling detection and enumeration of them. Staphylococcus aureus isolates were classified from culture isolation as either methicillin resistant or susceptible using cefoxitin disk diffusion testing. The photoacoustic method enumerates bacterial cells before and after treatment with antibiotics. Decreasing counts of bacteria after treatment indicate susceptible strains. We quantified the bacterial cells in the treated and untreated samples.ResultsUsing k-means clustering on the data, we achieved 100% concordance with the classification of Staphylococcus aureus resistance using culture.DiscussionPhotoacoustics can be used to differentiate methicillin resistant and susceptible strains of bacteria from ocular infections. This method may be generalized to other bacterial species using appropriate bacteriophages and testing for resistance using other antibiotics.

Purpose: This study aimed to evaluate the outcomes of astigmatic correction by single-step transepithelial photorefractive keratectomy (TransPRK) and femtosecond-assisted laser in-situ keratomileusis (Femto-LASIK) surgeries. Methods: A total of 218 subjects received TransPRK or Femto-LASIK surgery for the treatment of myopia and astigmatism (−2.25 to −0.25 D). Refraction errors and uncorrected (UDVA) and corrected distance visual acuity (CDVA) were examined before and at 3 months after surgery. Astigmatism changes were assessed by vector analysis. Results: Preoperative parameters of the TransPRK group were similar to the Femto-LASIK group. UDVA and CDVA at 3 months were similar between both groups. Manifest refraction (MR) spherical equivalent in the TransPRK group (0 ± 0.20 D) was slightly lower compared with the Femto-LASIK group at 3 months (0.11 ± 0.25 D, P = 0.001). MR cylinder was -0.06 ± 0.19 D in the TransPRK group and -0.02 ± 0.15 D in the Femto-LASIK group at 3 months (P = 0.135). The index of success (IS) was 0.15 ± 0.36 in the TransPRK group and 0.06 ± 0.17 in the Femto-LASIK group (P = 0.125). The correction index (CI) was 1.03 ± 0.19 in the TransPRK group and 1.01 ± 0.11 in the Femto-LASIK group (P = 0.815). Conclusion: For low to moderate myopic astigmatism, TransPRK provided a comparable astigmatic treatment effect as Femto-LASIK. Myopic astigmatism was both slightly overcorrected after TransPRK and Femto-LASIK surgeries.

PurposeWe aim to investigate the effect of sustained hyperglycemia on corneal epithelial wound healing, ocular surface and systemic immune response, and microbiome indices in diabetic mice compared to controls after alkaline chemical injury of the eye.MethodsCorneal alkaline injury was induced in the right eye of Ins2Akita (Akita) mice and wild-type mice. The groups were observed at baseline and subsequently days 0, 3, and 7 after injury. Corneal re-epithelialization was observed under slit lamp with fluorescein staining using a cobalt blue light filter. Enucleated cornea specimens were compared at baseline and after injury for changes in cornea thickness under hematoxylin and eosin staining. Tear cytokine and growth factor levels were measured using protein microarray assay and compared between groups and time points. Flow cytometry was conducted on peripheral blood and ocular surface samples to determine CD3+CD4+ cell count. Fecal samples were collected, and gut microbiota composition and diversity pattern were measured using shotgun sequencing.ResultsAkita mice had significantly delayed corneal wound healing compared to controls. This was associated with a reduction in tear levels of vascular endothelial growth factor A, angiopoietin 2, and insulin growth factor 1 on days 0, 3, and 7 after injury. Furthermore, there was a distinct lack of upregulation of peripheral blood and ocular surface CD3+CD4+ cell counts in response to injury in Akita mice compared to controls. This was associated with a reduction in intestinal microbiome diversity indices in Akita mice compared to controls after injury. Specifically, there was a lower abundance of Firmicutes bacterium M10-2 in Akita mice compared to controls after injury.ConclusionIn diabetic mice, impaired cornea wound healing was associated with an inability to mount systemic and local immune response to ocular chemical injury. Baseline and post-injury differences in intestinal microbial diversity and abundance patterns between diabetic mice and controls may potentially play a role in this altered response.

Purpose: The purpose of the study was to evaluate, as a pilot trial, safety and tolerability of CAM-101 10% and 30% topical ophthalmic fibrinogen-depleted human platelet lysate (FD hPL) solution in patients with dry eye disease (DED) secondary to graft-versus-host disease (GvHD) after 6 weeks of treatment. Design: A phase I/II, pilot, prospective, multicenter, randomized, double-masked clinical trial. Participants: Patients with DED secondary to GvHD. Methods: Sixty-four adult patients were stratified by “symptom severity” (Ocular Surface Disease Index [OSDI], ocular discomfort Visual Analog Scale (VAS), ocular symptom frequency, and use of artificial tears) and then randomized 1:1:1 to CAM-101 (FD hPL) at 10% or 30% concentration or an electrolyte (Plasma-Lyte A) vehicle control, 1 drop in both eyes, 4 times daily, for 42 days. After 42 days, control patients were offered 42 days of open-label treatment with 30% FD hPL. Main Outcome Measures: Primary outcome safety measures were ocular and systemic adverse events and the number of patients in each group with clinically significant change from normal to abnormal in any ocular findings. Secondary outcomes were changes from baseline to day 42 in ocular discomfort, OSDI, fluorescein corneal staining, and lissamine green conjunctival staining relative to the vehicle control. The ocular symptom frequency was assessed on a 100-point VAS. Results: FD hPL 10% and 30% were safe and well tolerated. Relative to the vehicle control, significant decreases from baseline to day 42 were seen in the FD hPL 30% group with regard to ocular discomfort (mean decrease = −18.04; P = 0.018), frequency of burning/stinging (−20.23; P = 0.022), eye discomfort (−32.97; P < 0.001), eye dryness (−21.61; P = 0.020), pain (−15.12; P = 0.044), photophobia (−24.33; P = 0.0125), and grittiness (−20.08; P = 0.0185). Decreases were also seen for itching and foreign body sensation, though not statistically significant. Improvements were seen in tear breakup time (mean increase = 1.30 seconds; P = 0.082) and the investigator’s global evaluation 4-point scale (mean decrease = −0.86; P = 0.026). Corneal fluorescein staining was not improved. The OSDI had a mean decrease of −8.88 compared to the vehicle, although not statistically significant. Conclusions: Fibrinogen-depleted human platelet lysate appears to be well tolerated, with no significant toxicity at concentrations of 10% and 30%. These initial data suggest some efficacy, especially for subjective outcome measures relative to baseline assessments and treatment with the vehicle, but larger studies are needed to confirm these effects.

Purpose: To examine the clinical presentation, management, and outcomes of culture and polymerase chain reaction (PCR) negative cases of infectious keratitis. Methods: In this retrospective case series, we evaluated the laboratory and medical records of culture- and PCR-negative cases (2016–2020) reported to a tertiary care center, which were presumed to be infectious keratitis on the basis of clinical history and presentation. Results: A total of 121 cases with culture-negative keratitis were included in this study. The mean age of the patients was 48.42 ± 1.89 years, and 53.72% were female. At presentation, the presumed etiology was viral in 38.01%, bacterial in 27.27%, fungal in 8.26%, Acanthamoeba in 6.61%, and unlisted in 28.92% of cases. The most common risk factors were a previous history of ocular surface diseases (96.69%) and contact lens use (37.19%). In total, 61.98% of the patients were already on antimicrobial medication at presentation. The initial management was altered in 79 cases (65.29%) during the treatment course. Average presenting and final (post-treatment) visual acuities (VA) were 0.98 ± 0.04 (LogMAR) and 0.42 ± 0.03 (LogMAR), respectively. A significantly higher frequency of patients with a final VA worse than 20/40 (Snellen) had worse VA at initial presentation (p < 0.0001). A history of ocular surface disease, cold sores, and recurrent infection (p < 0.05) were more commonly associated with a presumed diagnosis of viral keratitis. The patients with presumed bacterial etiology were younger and had a history of poor contact lens hygiene (p < 0.05). Conclusions: We observed a distinct difference in clinical features among patients with culture-negative and PCR-negative keratitis managed for presumed viral and bacterial infections. Although there was significant variability in presentation and management duration in this cohort, the visual outcomes were generally favorable.

Purpose: Systemic doxycycline has been prescribed to reduce inflammation and enhance corneal healing in bacterial keratitis. Topical autologous serum drops (ASD) containing doxycycline following oral supplementation may additionally confer an anti-bacterial effect. The potential of this supplementation was evaluated by determining the in vitro susceptibility of bacterial keratitis isolates to doxycycline. Methods: The minimum inhibitory concentrations (MICs) of doxycycline against 100 bacterial keratitis isolates were determined using Etests. Twenty-seven Staphylococcus aureus, ten coagulase-negative Staphylococci, six Streptococcus pneumoniae, seven viridans group streptococci, seven other Gram-positive bacteria, nineteen Pseudomonas aeruginosa, eight Serratia marcescens, four Moraxella spp., two Haemophilus spp., and ten other Gram-negative bacteria isolates were tested. MICs of doxycycline were compared to a serum standard concentration of doxycycline (SSCD) of 4 µg/mL and concentrations that would be found in 50% and 20% serum component clinical preparations of ASD, corresponding to 50% SSCD (2 µg/mL) and 20% SSCD (0.8 µg/mL), respectively. MICs equal to or less than these values were used to deem a bacterial isolate susceptible. Results: For Gram-positive bacteria, susceptibilities to SSCD, 50% SSCD, and 20% SSCD were 86%, 65%, and 60%, respectively. For Gram-negative bacteria, susceptibilities to SSCD, 50% SSCD, and 20% SSCD were 37.2%, 23.3%, and 11.6%, respectively. Chi-squared analyses comparing Gram-positive and Gram-negative susceptibilities showed significantly greater susceptibility of Gram-positive bacteria at all three tested MICs (

PurposeThis retrospective study aimed to identify the key factors influencing postoperative refraction after small-incision lenticule extraction (SMILE) using information gain.MethodsThis study comprised 2,350 eyes of 1,200 patients who underwent SMILE using a Visumax 500-kHz femtosecond laser (Carl Zeiss Meditec AG) in three ophthalmic centers: Tianjin Eye Hospital (center A), Jinan Mingshui Eye Hospital (center B), and Qingdao Eye Hospital (center C). Anterior segment features, including corneal curvature and central corneal thickness (CCT), were obtained from Pentacam HR (Oculus, Wetzlar, Germany). Information gain was calculated to analyze the importance of features affecting postoperative refraction.ResultsPreoperative and postoperative mean spherical equivalent (SE) refraction were −5.00 (−6.13, −3.88) D and 0.00 (−0.25, 0.13) D, respectively. None of the patients lost more than two lines of corrected distance visual acuity. The safety index was 1.32 ± 0.24, 1.03 ± 0.08, and 1.13 ± 0.16 in centers A, B, and C, respectively. The efficacy index was 1.31 ± 0.25, 1.02 ± 0.08, and 1.13 ± 0.17 in centers A, B, and C, respectively. At least 95% of the eyes were within ±1.00 D of the attempted correction. Postoperative refraction was related to preoperative spherical diopter refraction (r = 0.369, p < 0.001), preoperative SE (r = 0.364, p < 0.001), maximum lenticule thickness (r = −0.311, p < 0.001), preoperative uncorrected distance visual acuity (r = 0.164, p < 0.001), residual stromal thickness (r = 0.139, p < 0.001), preoperative mean anterior corneal curvature (r = −0.127, p < 0.001), preoperative flattest anterior corneal curvature (r = −0.122, p < 0.001), nomogram (r = −0.100, p < 0.001) and preoperative CCT (r = −0.058, p = 0.005).ConclusionsSMILE was considered a safe and effective procedure for correcting myopia. Based on information gain, postoperative refraction was influenced by preoperative mean anterior corneal curvature, CCT, refraction, and residual stromal thickness.

Abstract Background To assess the corneal stress-strain index (SSI), which is a marker for material stiffness and corneal biomechanical parameters, in myopic eyes. Methods A total of 1054 myopic patients were included in this study. Corneal visualisation Scheimpflug technology was used to measure the SSI. Corneal biomechanics were assessed using the first and second applanation times (A1-and A2-times); maximum deflection amplitude (DefAmax); deflection area (HCDefArea); the highest concavity peak distance (HC-PD), time (HC-time), and deflection amplitude (HC-DefA); integrated radius (IR); whole eye movement (WEM); stiffness parameter (SP-A1;, biomechanically corrected intraocular pressure (BIOP); and Corvis biomechanical index (CBI). Scheimpflug tomography was used to obtain the mean keratometery (Km) and central corneal thickness (CCT). According to the spherical equivalent (SE) (low myopia: SE ≥ − 3.00D and high myopia: SE ≤ − 6.00D.), the suitable patients were divided into two groups. Results The mean SSI value was 0.854 ± 0.004. The SSI had a positive correlation with A1-time ((r = 0.272), HC-time (r = 0.218), WEM (r = 0.288), SP-A1 (r = 0.316), CBI (r = 0.199), CCT (r = 0.125), bIOP (r = 0.230), and SE (r = 0.313) (all p-values

Abstract The coronavirus disease 2019 pandemic has led to widespread change as public health strategies for containment have emphasized social distancing and remaining at home. These policies have led to downscaled clinic volumes, cancellation of elective procedures, enhanced personal protective strategies in the clinic, and adoption of telemedicine encounters. We describe the evidence-based practical approach taken in our ophthalmology department to continue delivering eye care during the pandemic by rescheduling visits, enhancing clinic safety, and adopting virtual video encounters.

Introduction. The Global Delphi Panel of Keratoconus (KC) and Ectatic Diseases formulated management guidelines for KC in 2015. The aim of this study was to evaluate management outcomes in pediatric KC. Materials and Methods. Prospective, interventional study was conducted at a tertiary care hospital including KC patients aged

Purpose. To evaluate whether unilateral crosslinking (CXL) and conservative follow-up of the fellow eye is an acceptable management strategy in patients with keratoconus (KC). Methods. Seventy-nine fellow eyes of KC subjects that initially underwent unilateral CXL were included. Thirty fellow eyes ultimately received CXL (group 1) whereas 49 fellow eyes were followed (group 2). Best spectacle corrected visual acuity (BSCVA) and corneal tomographic parameters were collected in all eyes preoperatively and at the last follow-up. Results. Subjects who received CXL in the fellow eye (group 1) were younger than subjects who did not (group 2, p=0.026). Group 1 eyes had higher baseline K1 (p=0.026), K2 (p=0.006), Km (p=0.01), and Kmax (p=0.002) compared to group 2 eyes. Amongst the 49 naïve fellow eyes (group 2), 19 eyes showed evidence of progression. Progressing naïve eyes had higher baseline K1, K2, Km, and Kmax (p 45.1D, Km > 44.3D, Kmax > 47.9D, astigmatism > 1.4D, pachymetry at the pupil

Significance: Our study found that SP-A1 (stiffness parameter at time of first applanation) was statistically different between post-laser-assisted subepithelial keratomileusis (LASEK) and post-small incision lenticule extraction (SMILE) eyes. The stiffness of keratoconus was lower than that of post-refractive surgery corneas.Purpose: To compare corneal biomechanics among post-SMILE, post-LASEK, and keratoconic eyes.Methods: In this retrospective study, 36 eyes of 36 patients after SMILE, 36 eyes of 36 patients after LASEK, and 36 eyes of 36 patients with keratoconus with matching (±5 μm) central corneal thickness (CCT) were examined using Scheimpflug corneal topography (Pentacam HR) and dynamic Scheimpflug analyzer (CorVis ST). Mixed linear model analysis with Bonferroni-adjusted post-hoc comparisons was performed to compare the differences in corneal biomechanics and topographic parameters among the three groups with the CCT and the bIOP (intraocular pressure with biomechanical correction) as the random factor.Results: All groups had comparable CCT at baseline. The bIOPs between the three groups were comparable. The mean values of the Belin/Ambrósio Deviation (BAD-D) in the keratoconus group were significantly higher than those of the SMILE (post hoc p < 0.001) and LASEK groups (post hoc p < 0.001). The SP-A1 in the keratoconus group was the lowest when compared with those of the SMILE (post hoc p = 0.003) and LASEK groups (post hoc p < 0.001). The SMILE group SP-A1 values were slightly lower than those of the LASEK group (post hoc p = 0.044).Conclusions: Keratoconus eyes were significantly softer when compared to post-refractive surgery corneas with comparable corneal thickness in terms of SP-A1 and BAD-D values, while the LASEK group may have the greatest stiffness. Post-SMILE and post-LASEK corneas showed significant differences in SP-A1.

Abstract Laser-assisted in situ keratomileusis (LASIK) is the most commonly performed laser refractive surgical technique worldwide for the treatment of myopia and myopic astigmatism. In recent years, small incision lenticule extraction (SMILE) has emerged as a promising alternative to LASIK, requiring only a single femtosecond laser to create an intrastromal lenticule, which is then removed via a small incision. The technique obviates the need for a corneal flap. A number of published studies have compared the two techniques in terms of visual, refractive and ocular surface outcomes. This review compares the clinical outcomes between LASIK and SMILE in treating myopia and myopic astigmatism based on studies published in the last 5 years. Twenty-two studies were included, all of which were observational in nature. Results suggest that the two techniques have comparable visual outcomes in terms of safety, efficacy and predictability, although recovery in visual acuity may be slower in SMILE-treated than LASIK-treated eyes. SMILE is found to result in less severe postoperative dry eye symptoms and faster recovery of corneal sensitivity than LASIK. It is important to note, however, that the SMILE technique is limited by the lack of a cyclotorsion-compensation system and option for customized treatment profile. The heterogeneity of results in this review may be attributable to the use of different LASIK platforms in different studies. Few studies compared the outcomes regarding severity of myopia. Future prospective randomized controlled trials with a larger sample size and longer follow-up period will be highly beneficial for progress in this field.

Fungal keratitis (FK) can be challenging to diagnose and treat. In this retrospective case series, FK cases presenting at the University of Pittsburgh Medical Center, Pennsylvania, USA, from 2015 to 2021 were reviewed for ocular risk factors, clinical presentation, management, and outcomes. Twenty-eight cases of FK were included. The median presenting age was 58.5 (18.5) years, and the median symptom duration prior to presentation was 10 (35.8) days. Predisposing ocular risk factors included contact lens use (67.9%), recent ocular trauma/abrasion (42.9%), and history of ocular surgery (42.9%). The median presenting visual acuity (VA) was 1.35 (1.72) LogMAR. About half presented with a central ulcer (42.9%), large infiltrate (6.7 (6.3) mm2), corneal thinning (50.0%), and hypopyon (32.1%). The majority of isolated fungal species were filamentous (75.0%). Most common antifungal medications included topical voriconazole (71.4%) and natamycin (53.6%) drops and oral voriconazole (64.3%). Surgical management was necessary in 32.1% of cases and enucleation in one case. Defect resolution occurred in 42.5 (47.0) days, and median final VA was 0.5 (1.84) LogMAR. Features associated with poor final visual outcomes included poor initial VA (p < 0.001) and larger defect size (p = 0.002). In conclusion, unlike prior studies in the northeast region of the USA, FK was commonly caused by filamentous fungi, and antifungal management most often consisted of topical and oral voriconazole.